Technical Field
This application relates to methods for treating and/or for slowing the progression of myopia, particularly in children. These methods comprise administering a member of a selected group of anticholinergic zwitterions.
Description of Background Art
Myopia, also known as nearsightedness, is a common ocular disorder in humans. In the United States and Europe, myopia affects from 25% to 60% of older adults. The incidence is much higher in East Asia, where it can affect up to 80% of young adults. It typically occurs first in childhood.
Unfortunately, myopia is associated with increased risk of very serious conditions, among them glaucoma, detachment of the retina and myopic macular degeneration. Further, the incidence of myopia appears to be on the rise. It would therefore be of interest to develop an effective treatment of myopia, particularly one that can slow the progression of myopia, especially severe myopia, in children.
A review article on the present status of myopia treatment has been published recently by Jeffrey Cooper, Erica Schulman and Nadine Jamal. See Cooper et al., “Current Status on the Development and Treatment of Myopia”, Optometry 2012 May 31, 83(5), pp. 174-99, published by the American Optometric Association online.
According to Cooper et al., myopia is classified in three groups: pathologic (usually before age six), school age (between the ages of 6 and 18) and adult onset. Myopia progression is greatest in young children. Treatments include spectacle correction (bifocals and multifocal lenses), contact lenses (single vision contact lenses, orthokeratology, multifocal soft contact lenses), atropine and pirenzepine. Generally speaking, bifocals and progressive lenses have not been very effective in slowing the progression of myopia in children. While orthokeratology and soft contact lenses have recently shown some success, the progression of myopia has been most effectively slowed by topical atropine, which is known as an anticholinergic/mydriatic agent. See also Chua et al., “Atropine for the Treatment of Childhood Myopia”, Ophthalmology 2006; 113; 2285-2291, American Academy of Ophthalmology, published by Elsevier Inc.; Chia et al., “Atropine for the Treatment of Childhood Myopia: Safety and Efficacy of 0.5%, 0.1% and 0.01% Doses (Atropine for the Treatment of Myopia 2), Ophthalmology 2012; 119; 347-354, American Academy of Ophthalmology, published by Elsevier Inc.; and Fang et al., “Prescription of atropine eye drops among children diagnosed with myopia in Taiwan from 2000 to 2007: a nationwide study”, Eye (2013), 1-7, Macmillan Publishers.
Atropine was used as early as the nineteenth century for slowing myopia progression, but fell into disfavor after the turn of the twentieth century. However, interest revived in using topical atropine to slow myopia progression in the 1960's and has continued since that time. Progressively lower concentrations have been tested and found effective. In the ATOM2 studies detailed by Chia et al. referenced above, the mean myopia progression at 2 years was as follows: for 0.5% atropine, 0.15 D/year; for 0.1% atropine, 0.19 D/year; and for 0.01% atropine, 0.24 D/year. Although no serious adverse events were reported, there appears to be a bias against atropine in the art because of atropine's possible side effects.
The possible side effects of atropine can include dry mouth, photophobia, blurred vision, urinary hesitancy and retention, decreased sweating, drowsiness, dizziness, restlessness, irritability, disorientation, hallucinations, tachycardia and cardiac arrhythmias, nausea, constipation, and severe allergic reactions, which often limit its clinical use, and even topical anticholinergics can cause the same unwanted side effects. Glycopyrrolate is among the quaternary ammonium anticholinergics, which have reduced CNS-related side effects as they cannot cross the blood-brain barrier; however, because glycopyrrolate is eliminated mainly as unchanged drug or active metabolite in the urine, its administration is problematic in young or elderly patients and especially in uraemic patients.
Pirenzepine, a M1-selective antagonist previously used to treat gastric ulcers, does not have mydriatic properties, but has been found effective as a 2% ophthalmic gel in slowing the progression of myopia in a group of school-aged children, although not as successfully as topical atropine. Moreover, pirenzepine is not approved by the FDA.
In view of the foregoing, it is apparent that there is need for an alternative pharmacological approach to the treatment of myopia, particularly for slowing the progression of myopia, especially severe myopia, in school-age children or for treating myopia in adults which does not utilize topical atropine or pirenzepine.